Discovery of Yellow FeverVirus-Specific Epitopes for Development of an Accurate SerodiagnosticAssay Abstract Antibodiestomanypathogenicvirusescanbedetectedinblood,serumand/orsaliva.Amongthese aremanyarboviruses,thatshareendemicregionsinthewesternhemisphereandinotherpartsofthe world.Theseincludetherelatedflavivirusesyellowfevervirus(YFV),denguevirus(DENV),Zikavirus (ZIKV)andWestNilevirus(WNV)aswellasthealphaviruschikungunyavirus(CHIKV).Antibodiesto thesevirusesareoftencross-reactive,makingdiagnosticsforaparticularviruschallenging.Thecurrent outbreak of yellow fever in Brazil and the high mortality associated with this disease as well as the recent history of outbreaks in South America and Africa create an urgent need for YFV-specific serodiagnostics,toaidcontrolofthespreadofyellowfever.Moreover,suchdiagnosticswouldfacilitate clinical and public health efforts against these and other, related arboviruses. We propose a novel strategytodevelopmethodsforspecificandsensitivedetectionofantibodiesagainstYFVthatdonot crossreactwithotherarboviruses.Wewillemployaninnovative,comprehensiveproteomicapproach withauniqueserumsamplecollectionthatwillallowdiscoveryandvalidationofspecificbiomarkers capable of distinguishing YFV from other arboviruses. This will allow us to develop a specific and sensitivetestforYFVinfectioninPhaseIIofthisproject.Apractical,sensitiveandspecifictestforYFV infection is a high priority goal due to the recent outbreak of yellow fever in Brazil, possible future outbreaksandthelikelyspreadofyellowfevertosouthernUSstatesborderingtheGulfofMexicoand PuertoRicowhereAedesspp.mosquitosmightrapidlyspreadtheinfection.